The use of ECMO in conjunction with CPR, a technique known as ECPR, has been shown to reduce central nervous system (CNS) damage, improve brain function after recovery, and result in survival-to-hospital- discharge rates up to 40%. A limiting factor for widespread adoption of ECPR is the need for a simple automatic perfusion system that is inherently safe, and provides full support with minimal operator intervention. Developed under SBIR funding (HL091616), MC3's patented technologies have been combined to form a compact, highly portable, safe and simple to use automatic perfusion system (APS). This device will lower the barriers for implementation of emergent ECPR and facilitate expanded use of these procedures resulting in improved outcomes for refractory cardiac arrest. The APS system is also envisioned as a tool for salvaging donor organs after cardiac death (DCD). The user requirements for DCD support and ECPR are equivalent, allowing broader application of the APS in the expanding field of extracorporeal support. In Phase I and II, a prototype was developed for use in bench and animal testing and customer evaluations. In vivo studies demonstrated restoration of cardiac function with ECPR after 30 minutes of untreated ventricular fibrillation. Additional studies with controlled and uncontrolled DCD animal models confirmed device functionality and demonstrated conditioning of organs to transplant status following extended periods of warm ischemia up to 60 minutes. Paramedical personnel were trained on the use of MC3 system, and assisted in animal studies to evaluate the usability of the system. The goal of this Phase IIb NHLBI Bridge application is to advance the simple automatic perfusion system developed in Phase I/II to a commercial product for ECPR. We will capture critical feedback from users and consolidate electronics to improve safety and usability. The system will undergo complete verification and validation testing to prepare for regulatory submission. In vivo studies will be performed to assess device functionality and durability. At the end of Phase IIb we will have a highly integrated cardio-pulmonary support system for use in ECPR with fully automated regulation of flow, oxygen, CO2 and temperature to support controlled reperfusion strategies, while providing stable, auto-regulated perfusion. We anticipate this APS device will lower the barriers for implementation of emergent ECPR, and will result in expanded acceptance of these procedures resulting in greatly improved ECPR outcomes and greater availability of donor organs if resuscitation is not possible.